WASHINGTON — The FDA approved lorlatinib (Lorbrena) to treat patients with metastatic, anaplastic lymphoma kinase (ALK)-positive non—small-cell lung cancer (NSCLC), as detected by an FDA-approved test.
Lorlatinib, a third-generation oral ALK inhibitor, first received accelerated approval as a second- or third-line treatment in this population in November 2018. With this latest indication, the drug has been upgraded for use as first-line therapy, so long as the patient’s cancer was detected using a companion diagnostic tool, the Ventana ALK CDx Assay.
This approval was based on results from the phase III CROWN trial, a randomized, multicenter, open-label, active-controlled trial that recruited 296 patients with metastatic ALK-positive NSCLC who had not received prior systemic therapy for metastatic disease — patients were randomized to either lorlatinib 100 mg orally once daily (n=149) or crizotinib 250 mg orally twice daily (n=147). The trial results were published in The New England Journal of Medicine.
“The percentage of patients who were alive without disease progression at 12 months was 78% (95% confidence interval [CI], 70 to 84) in the lorlatinib group and 39% (95% CI, 30 to 48) in the crizotinib group (hazard ratio for disease progression or death, 0.28; 95% CI, 0.19 to 0.41; P<0.001),” CROWN researchers Alice T. Shaw, MD, PhD, of Massachusetts General Hospital in Boston, and colleagues reported.
The CROWN trial also assessed central nervous system (CNS) involvement in all patients, the FDA noted. “There were 17 patients in the lorlatinib arm and 13 in the crizotinib arm with measurable CNS lesions based on baseline brain imaging. Among these patients, the intracranial [overall response rate] ORR, as assessed by the [blinded independent central review] BICR, was 82% (95% CI: 57, 96) in the lorlatinib arm and 23% (95% CI: 5, 54) in the crizotinib arm. The duration of intracranial response was ≥ 12 months in 79% and 0% of patients in the lorlatinib and crizotinib arms, respectively.”
Common adverse events associated with lorlatinib, including Grade 3-4 laboratory abnormalities, included edema, peripheral neuropathy, weight gain, cognitive effects, fatigue, dyspnea, arthralgia, diarrhea, mood effects, hypercholesterolemia, hypertriglyceridemia, and cough.
John McKenna, Associate Editor, BreakingMED™
Cat ID: 24
Topic ID: 78,24,730,24,192,725,925
